Long COVID Biomarker Atlas
Molecular, metabolic, and immunological alterations reported in post-acute sequelae of COVID-19 (PASC / long COVID) compared to healthy controls and fully recovered individuals.
Literature Overview
Synthesized from systematic reviews and primary omics studies published through 2025. No single biomarker defines long COVID; a multi-system profile is emerging.
Immune & Inflammatory Dysfunction
Persistent low-grade inflammation early post-infection, with evidence of immune exhaustion or suppression at later timepoints. Elevated IL-6, TNF-α, CRP, and sCD14 are among the most replicated findings.
Metabolic & Mitochondrial Impairment
Reduced amino acid metabolism, depleted ceramides, elevated TCA cycle intermediates, and reduced ATP — consistent with mitochondrial dysfunction and impaired energy production in fatigue-dominant phenotypes.
Endothelial, Coagulation & Vascular
Elevated D-dimer, fibrinogen, von Willebrand factor, and markers of platelet hyperactivation. Microclot formation and impaired fibrinolysis have been documented in post-acute COVID cohorts.
Searchable Alterations Database
Filter by category or direction. Comparison groups: HC = healthy controls (SARS-CoV-2 unexposed); R = recovered without persistent symptoms.
Temporal dynamics matter
Biomarker patterns evolve over months. Early long COVID may show low-grade inflammation (elevated IL-6, CRP), while at 6+ months some cohorts show reduced pro-inflammatory cytokines compared to recovered individuals — suggesting immune exhaustion rather than normalization (Kallaste et al., 2025). Recovered individuals without symptoms may still show metabolomic alterations vs. never-infected controls at 12 months post-infection (Saito et al., 2024).
Related atlases: All Atlases · PACVS · ME/CFS · Lyme · Gulf War Illness
| Marker / Metabolite | Direction | Category | vs. Comparison | Associated Symptoms | Key Reference |
|---|
Category Deep Dives
Pathway-level summaries from primary studies and systematic reviews.
🔥 Cytokines & Inflammatory Mediators
- IL-6 ↑ LC
- TNF-α ↑ LC
- IL-1α ↑ LC
- CRP ↑ LC
- sCD14 (monocyte activation) ↑ LC
- Flt-1 / sVEGFR-1 ↑ LC
- CCL4 (MIP-1β) ↑ at 3 mo
- CST5 (Cystatin D) ↑ at 6 mo
- Pro-inflammatory cytokines (late) ↓ vs R
- TGF-β ↑ pulmonary LC
⚡ Metabolites & Energy Pathways
- ATP (plasma) ↓ LC
- Serine ↓ LC
- Sarcosine ↓ LC
- Aspartate / Asparagine ↓ LC
- Glutamine / Arginine / Histidine ↓ LC
- TCA cycle intermediates (succinate, etc.) ↑ LC
- Kynurenine pathway metabolites ↑ LC
- Serotonin / Putrescine ↑ LC
- 5-Aminolevulinate / Porphobilinogen ↑ LC
- Uracil / Thymine ↓ LC
🩸 Coagulation & Vascular Markers
- D-dimer ↑ LC
- Fibrinogen ↑ LC
- von Willebrand factor (vWF) ↑ LC
- PAI-1 (plasminogen activator inhibitor) ↑ LC
- Platelet activation markers (P-selectin) ↑ LC
- Amyloid-fibrin microclots ↑ LC
- Resistin ↑ LC
- ICAM-1 / VCAM-1 ↑ LC
- Endothelial dysfunction markers ↑ LC
🧠 Neurological & Autoimmune Markers
- Neurofilament light chain (NfL) ↑ neuro LC
- GFAP (glial fibrillary acidic protein) ↑ neuro LC
- Autoantibodies (anti-IFN-α, anti-IFN-ω) ↑ LC
- Anti-GPCR autoantibodies ↑ LC
- Anti-nuclear antibodies Variable
- Complement activation (C3a, C5a) ↑ LC
- β2-microglobulin ↑ LC
🧬 Lipidomics & Proteomics
- Ceramides (plasma) ↓ LC
- Sphingolipid species Altered
- 447 lipid species profile Discriminant
- Complement & coagulation cascade proteins ↑ LC
- Acute phase proteins (SAA, AGP) ↑ LC
- Extracellular matrix remodeling proteins Altered
- Cortisol / DHEA ratio Altered
🦠 Viral Persistence & Microbiome
- SARS-CoV-2 spike protein (circulating) Detected in subset
- Persistent S1 spike antigen (plasma, ≤12 mo) ↑ Walt/Brigham 2023
- SARS-CoV-2 RNA (blood/tissue) Detected in subset
- SARS-CoV-2-specific CD8 T cells (activation) ↕ under investigation
- IFN-γ (SARS-CoV-2-specific T cell) ↕ stable/persistent
- Gut microbiome diversity ↓ LC
- Faecalibacterium prausnitzii ↓ LC
- Opportunistic pathogen abundance ↑ LC
- Microbial-derived metabolites (SCFAs) Altered
- EBV / HHV-6 reactivation markers Reported
Key References
Primary sources underpinning this atlas. Full reference lists available in each linked publication.